TY - JOUR
T1 - Helicobacter pylori virulence genes in the five largest islands of Indonesia
AU - Miftahussurur, Muhammad
AU - Syam, Ari Fahrial
AU - Makmun, Dadang
AU - Nusi, Iswan Abbas
AU - Zein, Lukman Hakim
AU - Zulkhairi,
AU - Akil, Fardah
AU - Uswan, Willi Brodus
AU - Simanjuntak, David
AU - Uchida, Tomohisa
AU - Adi, Pangestu
AU - Rezkitha, Yudith Annisa Ayu
AU - Subsomwong, Phawinee
AU - Nasronudin,
AU - Yamaoka, Yoshio
AU - Utari, Amanda Pitarini
N1 - Funding Information:
This report is based on work supported in part by grants from the National Institutes of Health (DK62813) (YY), and Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (24406015, 24659200, 25293104, 26640114, 15H02657 and 221S0002) (YY). This work was also supported by the Japan Society for the Promotion of Science (JSPS) Institutional Program for Young Researcher Overseas Visits and the Strategic Funds for the Promotion of Science and Technology from Japan Science and Technology Agency (JST).
Publisher Copyright:
© 2015 Miftahussurur et al.
PY - 2015/10/5
Y1 - 2015/10/5
N2 - Background: It remains unclear whether the low incidence of gastric cancer in Indonesia is due to low infection rates only or is also related to low Helicobacter pylori pathogenicity. We collected H. pylori strains from the five largest islands in Indonesia and evaluated genetic virulence factors. Methods: The genotypes of H. pylori virulence factors were determined by polymerase chain reaction (PCR)-based sequencing. Histological severity of the gastric mucosa was classified into 4 grades, according to the updated Sydney system. Results: A total of 44 strains were analyzed. Forty-three (97.7 %) were cagA-positive: 26 (60.5 %) were East-Asian-typecagA, 9 (20.9 %) were Western-type-cagA, and 8 (18.6 %) were novel ABB-type, most of which were obtained from Papuan. EPIYT sequences were more prevalent than EPIYA sequences (P = 0.01) in the EPIYA-B motif of all types of cagA. The majority of cagA-positive strains (48.8 %, 21/43) had a 6-bp deletion in the first pre-EPIYA region. Subjects infected with East-Asian-type-cagA strains with a 6-bp deletion had significantly lower inflammation and atrophy scores in the corpus than those infected with Western-type-cagA strains (both P = 0.02). In total, 70.4 % of strains possessed the vacA s1m1 genotype and 29.5 % were m2. All strains from peptic ulcer patients were of the iceA1 genotype, which occurred at a significantly higher proportion in peptic ulcer patients than that in gastritis patients (55.3 %, P = 0.04). The double positive genotype of jhp0562/â-(1,3)galT was predominant (28/44, 63.6 %), and subjects infected with this type had significantly higher inflammation scores in the corpus than those with the jhp0562 negative/â-(1,3)galT positive genotype (mean [median]; 1.43 [1] vs. 0.83 [1], P = 0.04). There were significant differences in cagA and pre-EPIYA cagA type, oipA status, and jhp0562/â-(1,3)galT type among different ethnic groups (P < 0.05). Conclusions: In addition to a low H. pylori infection rate, the low incidence of gastric cancer in Indonesia might be attributed to less virulent genotypes in predominant strains, which are characterized by the East-Asian-type-cagA with a 6-bp deletion and EPIYT motif, a high proportion of m2, dupA negative or short type dupA, and the jhp0562/â-(1,3) galT double positive genotype.
AB - Background: It remains unclear whether the low incidence of gastric cancer in Indonesia is due to low infection rates only or is also related to low Helicobacter pylori pathogenicity. We collected H. pylori strains from the five largest islands in Indonesia and evaluated genetic virulence factors. Methods: The genotypes of H. pylori virulence factors were determined by polymerase chain reaction (PCR)-based sequencing. Histological severity of the gastric mucosa was classified into 4 grades, according to the updated Sydney system. Results: A total of 44 strains were analyzed. Forty-three (97.7 %) were cagA-positive: 26 (60.5 %) were East-Asian-typecagA, 9 (20.9 %) were Western-type-cagA, and 8 (18.6 %) were novel ABB-type, most of which were obtained from Papuan. EPIYT sequences were more prevalent than EPIYA sequences (P = 0.01) in the EPIYA-B motif of all types of cagA. The majority of cagA-positive strains (48.8 %, 21/43) had a 6-bp deletion in the first pre-EPIYA region. Subjects infected with East-Asian-type-cagA strains with a 6-bp deletion had significantly lower inflammation and atrophy scores in the corpus than those infected with Western-type-cagA strains (both P = 0.02). In total, 70.4 % of strains possessed the vacA s1m1 genotype and 29.5 % were m2. All strains from peptic ulcer patients were of the iceA1 genotype, which occurred at a significantly higher proportion in peptic ulcer patients than that in gastritis patients (55.3 %, P = 0.04). The double positive genotype of jhp0562/â-(1,3)galT was predominant (28/44, 63.6 %), and subjects infected with this type had significantly higher inflammation scores in the corpus than those with the jhp0562 negative/â-(1,3)galT positive genotype (mean [median]; 1.43 [1] vs. 0.83 [1], P = 0.04). There were significant differences in cagA and pre-EPIYA cagA type, oipA status, and jhp0562/â-(1,3)galT type among different ethnic groups (P < 0.05). Conclusions: In addition to a low H. pylori infection rate, the low incidence of gastric cancer in Indonesia might be attributed to less virulent genotypes in predominant strains, which are characterized by the East-Asian-type-cagA with a 6-bp deletion and EPIYT motif, a high proportion of m2, dupA negative or short type dupA, and the jhp0562/â-(1,3) galT double positive genotype.
KW - Helicobacter pylori
KW - Indonesia
KW - Virulence factors
UR - http://www.scopus.com/inward/record.url?scp=84942874733&partnerID=8YFLogxK
U2 - 10.1186/s13099-015-0072-2
DO - 10.1186/s13099-015-0072-2
M3 - Article
AN - SCOPUS:84942874733
SN - 1757-4749
VL - 7
JO - Gut Pathogens
JF - Gut Pathogens
IS - 1
M1 - 26
ER -
